HELP

If you would like to receive a free information packet** or have questions about mesothelioma, call us at:

Toll-Free 1-877-FOR MESO (367-6376)

**Packet includes information on specialists, treatments, clinical trials,
cancer links, and how to access legal and financial resources. You will
be contacted by a Mesothelioma Web co-ordinator who will be available
to discuss questions you might have.

NEWS

Studies Find No Evidence That SV40 is Related to Human Cancer

Two upcoming studies by scientists at the National Cancer Institute
(NCI), one of the National Institutes of Health, provide further evidence
that exposure to simian virus 40 (SV40) is not associated with cancer
in humans. Some U.S. polio vaccines administered from 1955-1962 were
accidentally contaminated with SV40 because the vaccines were grown in
monkey kidney tissue. Before the discovery of the virus led to changes
in vaccine manufacture, millions of Americans received SV40-contaminated
polio vaccines. This has been a significant public health concern, as
SV40 has been shown to cause cancer in experimental animals. However,
studies in humans have not proved conclusive.

Because some laboratory studies report that SV40 DNA can be detected
in various childhood tumors, scientists led by Eric Engels, M.D., M.P.H.,
an investigator in NCI's Division of Cancer Epidemiology and Genetics,
evaluated cancer risk of 54,796 U.S. children whose mothers received
polio vaccine during pregnancy that may have been contaminated with SV40.
Engels and colleagues hypothesized that mothers who were vaccinated against
polio before 1963 might have become infected with SV40 by this route
and transmitted the virus to their children. In animals, SV40 is most
likely to cause cancer when infection occurs during infancy. The scientists
wondered whether transmission of infection from a mother to her child
during pregnancy or soon after birth might be related to the later development
of childhood cancer.

The researchers compared cancer risk in children whose mothers received
pre-1963 polio vaccine with cancer risk in children whose mothers did
not receive pre-1963 polio vaccine. They also measured SV40 antibodies
in the mothers of 50 of these children who developed cancer and the mothers
of 200 children without cancer. One of this study's strengths is the
researchers' use of two different means of detecting SV40 antibodies,
which are produced by exposure to or infection with the virus. The first
method, called a plaque neutralization assay, has long been considered
the gold standard. They also used a virus-like particle assay, a newer
test with high sensitivity and specificity, allowing researchers to distinguish
between SV40 antibodies and those against other related viruses.

Interestingly, the investigators found that the incidence of neural
tumors and hematologic malignancies was roughly 2.5 times higher in children
whose mothers received pre-1963 vaccine than in children whose mothers
did not. However, the pattern of cancers in children whose mothers received
the vaccine was not what would be predicted if SV40 caused cancer: the
types of cancers varied and did not correspond to the types in which
SV40 DNA has reportedly been detected. "It was notable that only
one brain tumor of the types in which SV40 DNA has reportedly been detected--an
ependymoma--was observed, and that was in a child whose mother had not
received pre-1963 polio vaccine," explained Engels. "More cases
of the types of cancer hypothesized to be linked to SV40--for example
ependyomas, choroid plexus tumors, and osteosarcomas--would be expected
if SV40 were the cause of the tumors in these children." Additionally,
few women had antibodies to SV40 by either of the antibody tests, and
there was no consistent relationship between the development of SV40
antibodies during pregnancy and cancer in children.

The scientists acknowledge that the small number of children and the
number of individual cancer types seen were limitations. Nonetheless,
as Engels summarized, "Overall, these results argue against an important
role for SV40 in childhood cancers."

In the second study, Engels and scientists at other institutions evaluated
cancer risk in veterans who were exposed to SV40 in an early U.S. Army
adenovirus vaccine given between 1959 and 1961. This is the first follow-up
study of recipients of SV40-contaminated adenovirus vaccine. The adenovirus
vaccine was administered to new military recruits, who experienced epidemics
of respiratory disease caused by adenovirus arising from crowded living
conditions during basic training. Like the polio vaccine, adenovirus
vaccine was grown in monkey kidney tissue. However, because adenovirus
cannot grow in such tissue without SV40 acting as a helper virus, almost
all batches of this vaccine probably contained SV40. The adenovirus vaccine
was given to Army recruits during two well-defined time periods, alternating
with three periods of non-use, during the period 1959-1961. This pattern
of exposure to SV40-contaminated adenovirus vaccine allowed for a rigorous
comparison of cancer risk in vaccine-exposed and unexposed servicemen.

The researchers used Veterans Administration and military records to
identify individuals with cancer and to classify them with respect to
receipt of the Army's adenovirus vaccine. The study included cases of
mesothelioma, brain tumors, and non-Hodgkin lymphoma, which are tumor
types previously hypothesized to be linked to SV40. Importantly, the
investigators did not find evidence that SV40-contaminated adenovirus
vaccine was associated with an increased risk for these cancers.

The authors noted some limitations of the study. There were only 10
mesothelioma cases and the numbers of cases for individual types of brain
tumors were small. These small numbers limit the study's statistical
power. Nonetheless, the numbers for all types of brain tumors combined,
and for non-Hodgkin lymphoma, were substantial. Additionally, most subjects
would also have received polio vaccine possibly contaminated with SV40.
However, not every dose of polio vaccine contained SV40, and exposure
to polio vaccine was not dependent on whether individuals received adenovirus
vaccine. Thus, while the widespread use of polio vaccine could have diluted
an association between adenovirus vaccine and cancer, this effect was
likely minor.

Engels concluded, "Our results should be reassuring to military
veterans of the 1950s and 1960s, some of whom received adenovirus vaccines.
This study did not find that their exposure to this vaccine was related
to an increased risk of cancer."

Although SV40 causes cancer in laboratory animals, substantial epidemiological
evidence has accumulated to indicate that SV40 likely does not cause
cancer in humans. However, additional laboratory research is needed to
better define methods for SV40 detection, as laboratory studies looking
for SV40 DNA in human tumors have offered conflicting results. There
is also a need to conduct additional studies evaluating cancer patients
and controls for antibodies to SV40, which would be present in cancer
patients if SV40 causes cancer.